(135f) One-Step Regioselective Synthesis of Clindamycin Palmitate By Immobilized Lipase

Li, Z., Tsinghua University
Ge, J., Tsinghua University
Liu, Z., Key Lab of Industrial Biocatalysis, Ministry of Education, Tsinghua University

Clindamycin is an established antibiotic with proven effectiveness against Gram-positive organisms and Gram-negative anaerobes and thus has been widely applied to treat diseases including infections of the respiratory tract, skin and soft-tissue. Clindamycin could be used as a first-line treatment option for the methicillin-resistant Staphylococcus aureus (MRSA).

However, the synthesis of clindamycin palmitate involves laborious steps of protection and deprotection and gives an overall yield below 50%. Here we report the first example of the one-step synthesis of clindamycin palmitate with high regioselectivity using immobilized Candida antarctica lipase B (Novozym 435) as the catalyst. The lipase catalyzed synthesis reached a conversion above 90% in 12 hours in an organic solvent. Characterized by 1H and 13C NMR, DEPT, HMQC, ESI-MS and FT-IR spectra, a nearly 100% regioselective acylation was confirmed occurred at the 2-hydroxyl of clindamycin. The enzymatic acylation of clindamycin at the solvent-free condition catalyzed by Novozym 435 and other types of novel immobilized lipase such as the lipase-inorganic crystal hybrid nanoflower will also be introduced in this presentation. In summary, the one-step regioselective synthesis of clindamycin palmitate with a high yield (>90%) and a high regioselectivity (~100%) greatly simplifies the synthesis by excluding the group protection/deprotection procedures and downstream purifications, which makes this enzymatic process very attractive for the manufacturing of clindamycin ester derivatives in pharmaceutical industry.